# World Trade Center Particulate Matter Induced Cardiorespiratory and Vascular Dysfunction:  a MultiOmic Approach

> **NIH ALLCDC U01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2024 · $598,794

## Abstract

SUMMARY
Particulate matter (PM) associated cardiorespiratory and vascular dysfunction (CaRVD) poses a significant
global health burden. The World Trade Center (WTC) destruction on September 11, 2001 led to an intense
deposition of particulate matter (WTC-PM) into aerodigestive system. WTC associated morbidities include
respiratory, gastrointestinal, chronic rhinosinusitis, cancer, mental health concerns and more recently a focus
has been on cardiovascular disease. Our proposal will investigate the development of WTC-cardiorespiratory
and vascular dysfunction (WTC-CaRVD) which is firmly within the purview of the James Zadroga 9/11 Health
and Compensation Act.
WTC-PM exposure causes heterogeneous obstructive airways disease (OAD) patterns, which include airway
hyperreactivity (AHR) and loss of FEV1. Early diagnosis and therapeutic options are few, in part due to our limited
understanding of their pathogenesis. While pulmonary vascular changes are classically thought to occur due to
the hypoxemia of late OAD, recent investigations show that vascular dysfunction occurs early in OAD. This
vascular hypothesis of OAD postulates that pulmonary vasculature remodeling leads to loss of lung function.
Early evidence of WTC-CaRVD includes increased prevalence of cardiovascular disease risk factors such as
metabolic syndrome, elevated pulmonary artery/aorta ratio, and cardiovascular biomarkers (such as CRP).
Murine models of WTC-PM exposure show inflammation, AHR both acutely and persistently and reflect what is
seen in FDNY 1st responders. Airway and cardiac remodeling were also persistent features of WTC-PM exposure
in our murine models. Therefore, we will focus on Heme Oxygenase-1 (HO-1), a mediator of oxidative stress,
known to stimulate collagen formation and is also induced after WTC-PM exposure. Furthermore, pathways and
mechanisms of WTC-CaRVD warrant further study and are the focus of our 5-year proposal.
Our HYPOTHESIS is that WTC-PM exposure causes WTC-CaRVD mediated by HO-1. First responders with
AHR will have features of WTC-CaRVD, and will demonstrate a unique biomarker profile compared to controls.
Innovative aspects of this application include novel imaging modalities and multiOmic
(radiome/metabolome/methylome) assessments. These hypotheses will be explored in three AIMs.
AIM 1, we will explore the translatability of our findings in the FDNY WTC cohort. AIM 2 will phenotype serum
biomarkers/metabolites, epigenetics, histology and in vivo imaging (echocardiography, MRI, and µPET/µCT) of
WTC-CaRVD. Furthermore, we will utilize mice genetically deficient in HO-1 and exogenously attenuate HO-1
in our murine WTC-PM model, AIM 2 and 3. AIM 3 will quantify end organ involvement and loss/gain of function
of HO-1 by myography and immunohistologic expression of vascular markers. Confirmation of the relevance of
the vascular and airway remodeling of WTC-PM associated AHR would allow us to then focus on early detection
and tailor our therapeutics in the W...

## Key facts

- **NIH application ID:** 10842218
- **Project number:** 5U01OH011855-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Anna Nolan
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2024
- **Award amount:** $598,794
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842218

## Citation

> US National Institutes of Health, RePORTER application 10842218, World Trade Center Particulate Matter Induced Cardiorespiratory and Vascular Dysfunction:  a MultiOmic Approach (5U01OH011855-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842218. Licensed CC0.

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